The Periodontal Diseases Research Center at the University of Pennsylvania seeks to acquire fundamental information on the nature of human periodontal diseases. The Center is currently focusing on "localized juvenile periodontitis" (LJP) as a model for delineating the earliest pathogenic events in the development of destructive periodontitis. While LJP is a relatively rare form of periodontal disease, it provides unique opportunities for multidisciplinary research on the initial phases of periodontal infections. At present, little is known about this critical period of host-parasite interaction; preventing and management of LJP (or any other form of periodontitis) will not be reliable until the first steps in the initiation of the disease process are understood. The Center has instituted a longitudinal study in families with LJP: epidemiologic data indicate that healthy children within these families are at-risk to developing LJP. Our strategy is to observe and study such children at quarterly intervals in anticipation that some will eventually come down with disease. When this occurs, we shall be in a position to intercept and describe the changes that characterize the transition from health to disease. The approach is to monitor local microbiological, immunological and inflammatory functions at preselected "target sites" (first permanent molars and incisors) that are most susceptible to LJP. Systemic immunological and leukocyte responses are also being documented to ascertain whether they are abnormal in these children. Of particular interest is the role of Actinobacillus actinomycetemcomitans (Aa): substantial data implicate Aa as a potential etiologic agent in LJP. Our study should clarify the dynamics and significance of this association and provide insights into roles of Aa leukotoxin, fimbriae and immunosuppressive factors as mechanisms of microbial virulence. The longitudinal study of the etiology of LJP will reveal new information on the pathobiology of the human gingival crevice and help explain why/how some bacteria successfully colonize and attack the host in this area. This knowledge will eventually translate into more effective ways of minimizing gingival/periodontal infections.